Many metal ions produce immunosensitization. Some trace elements are strong immunosensitzers and acute exposure to high local concentrations, or prolonged exposure to lower concentrations of metal in the lung or in contact with the skin, initiates the immunological process and leads to acute or chronic disease. Exposures to such metals in the workplace, or in everyday life have considerable health consequences to society.
Occupations with the highest risk are those involving processes that generate particulates, such as metal production and machining. In general, the risk of disease is proportional to the intensity and duration of exposure to the sensitivity-inducing metal.
Chronic beryllium disease (CBD) is a hypersensitivity granulomatous disease that predominantly affects the lungs. Because of its unique properties, beryllium has become widely used in a variety of industrial applications, such as inertial guidance systems, turbine rotor blades, laser tubes, rocket engine liners, springs, aircraft brakes and landing gear, ball bearings, injection and blow mold tooling, electrical contacts, automotive electronics, X-ray tube windows, spark plugs, electrical components, ceramic applications, gears, aircraft engines, oil and gas industries, welding electrodes, computer electronics, and golf clubs.
Common manifestations of CBD include the insidious onset of exertional dyspnea, nonproductive cough, fatigue, arthralgias, and chest pain. Nonpulmonary organs, including the skin, liver, spleen, myocardium, kidneys, salivary glands, and bone, may also be affected. Lung function tests may demonstrate restrictive, obstructive, or mixed physiology, usually with a decreased pulmonary diffusing capacity. Chest radiographs are often normal in detecting early disease. With progression, diffuse infiltrates culminating in end-stage fibrosis typically occur.
Measurement of lymphocyte proliferative responses to beryllium using either peripheral blood cells or cells obtained by bronchoalveolar lavage (BAL) is the standard method of documenting beryllium sensitivity. Detecting beryllium sensitivity has been useful not only as part of the diagnostic criteria for chronic beryllium disease but also, cross sectional studies demonstrated that detecting beryllium sensitivity is useful for the early identification of subclinical and clinical beryllium-induced disease. Perhaps even more important, detection of beryllium sensitization has been used as a bioassay for the detection of exposure to abnormal environmental conditions.
The standard method for performing the lymphocyte proliferation assay utilizes tritiated thymidine to measure DNA synthesis. This has been termed the Beryllium Lymphocyte Proliferation Test or BeLPT. BeLPT is now required by the Department of Energy of the United States as part of the CBD prevention program.
In the United States, an estimated 800,000 workers were considered to be at risk for developing CBD in 1978. Because of the sensitivity of the BeLPT in identifying excessive exposures, the number of workers at risk for development of CBD in the United States is probably considerably more, and there may be over one million workers worldwide who are at risk. Thus, CBD represents a unique use of lymphocyte proliferation testing (blood and lavage), for diagnosis, screening and surveillance. However, the widespread use of the BeLPT has been criticized by some because of the variability of the test, despite efforts to standardize the method. The practice of having two laboratories test split blood samples from a given individual is reported to identify more cases of beryllium sensitization than would have been the case for either laboratory alone.
Since the onset of disease is insidious aid prolonged exposure may accelerate progression, there has been widespread recognition of the utility of beryllium screening tests for at-risk populations. Because the tritiated thymidine method of determining lymphocyte proliferation is complex and requires radioactive materials and analysis over several days, a reliable method allowing for fast, accurate and non-invasive diagnosis, screening and surveillance is desired.